Asian Biomedicine Vol. 9 No. 3 June 2015; 379 - 385 DOI: 10.5372/1905-7415.0903.

407

Brief communication (Original)

Ephedrine and propofol for induction of general

anesthesia can decrease intraoperative hypothermia in
patients undergoing plastic and breast surgery: a
randomized, controlled trial
Thanist Pravitharangul, Wirakorn Koopinpaitoon, Rungruedee Kraisen, Rojnarin Komonhirun
Department of Anesthesiology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok
10400, Thailand

Background: Ephedrine has vasoconstrictive and mild β-adrenergic agonist effects that may be able to decrease
intraoperative core temperature hypothermia. However, its efficacy is still unclear.
Objectives: To determine the efficacy of ephedrine given during induction to maintain core temperature during
plastic and breast surgery under general anesthesia.
Materials and Methods: A prospective, randomized, double-blinded study was approved by our Institutional
Review Board and registered with the Thai Clinical Trials Registry as TCTR20141212002. We randomly assigned
30 patients to receive mixture of propofol and ephedrine (ephedrine group, n = 15) or a mixture of propofol and
normal saline (control group, n = 15) for induction of general anesthesia. The tympanic temperature (core
temperature before intubation), esophageal temperature (core temperature after intubation), index temperature
(peripheral temperature), systolic and diastolic blood pressure were compared between groups and baselines.
Results: During surgery, patients in ephedrine group showed better esophageal temperature maintenance than
those in the control group. Whereas systolic blood pressure in ephedrine group was significantly higher than
in the control group in early phase after induction.
Conclusions: A bolus dose of ephedrine given during induction can decrease core temperature loss during
plastic and breast surgery under general anesthesia.

Keywords: Ephedrine, general anesthesia, hypothermia, temperature

Intraoperative hypothermia is well known to cause
various complications during both intraoperative
and postoperative periods [1-3]. Much effort has been
devoted to improving core temperature preservation.
Because the main mechanism for the first hour of
heat loss during general anesthesia is redistribution
of heat from the central core to the periphery [4],
many approaches have been attempted to reduce
vasodilation and, by consequence, decrease core
temperature loss [5]. Ephedrine stimulates
norepinephrine release and also has mild β-adrenergic
agonist effects, which may be able to counteract
vasodilation. Its duration of action also provides
the possibility for it to be administered as a bolus
dose. An admixture of ephedrine and propofol
Correspondence to: Thanist Pravitharangul, Department of
Anesthesiology, Faculty of Medicine Ramathibodi Hospital,
Bangkok 10400, Thailand. E-mail: thanist.pra@mahidol.ac.th
had demonstrated more hemodynamic stability
when administered for induction [6, 7]. Therefore,
the mixture may be able to both preserve core
temperature and reduce hypotension caused by
propofol. This study was designed to determine the
efficacy of single bolus dose of ephedrine given during
induction of general anesthesia on preserving
esophageal temperature.
Materials and methods
The study was approved by Committee on Human
Rights Related to Research Involving Human
Subjects, Faculty of Medicine Ramathibodi Hospital,
Mahidol University and protocol of this study was
registered in Thai Clinical Trials Registry and coded
as TCTR20141212002. We recruited 30 patients in
Ramathibodi Hospital aged 18−70 years old with an
American Society of Anesthesiologist physical status
I−III who were scheduled to undergo plastic or breast
380 T. Pravitharangul, et al.
surgery with expected duration of surgery longer than
120 min. Signed written informed consent was obtained
from all patients. Patients with a tympanic temperature
more than 37.5°C, blood pressure at time of induction
more than 140/90 mmHg, BMI more than 30, thyroid
disease, receiving medications for hypertension, with
a risk of aspiration or expected difficult airway were
excluded. The patients with actual surgery time less
than 90 min, hand, wrist, forearm, or intraoral surgery
were also excluded. The patients were randomized
into an ephedrine group (n = 15) and control group
(n = 15) using a computer-generated randomization
list in a sealed envelope.
All patients received 7.5 mg of midazolam orally
before the scheduled time for surgery. Warmed
Ringer’s acetate (41°C) was used for intravenous fluid
supplementation in all patients. A skin temperature
probe was attached to the palmar side of index finger
of the noninfused arm and index temperature was
recorded. At time of induction all patients received
intravenous 50 μg of fentanyl. General anesthesia was
induced with a mixture of 2 mg/kg of propofol and
12 mg (6 mg/mL, total 2 mL) of ephedrine in ephedrine
group and mixture of 2 mg/kg of propofol and 2 mL of
normal saline in the control group. All induction agents
were prepared by another anesthesiologist who
was not involved in data collection and analysis. After
induction patients in both groups were ventilated with
2% sevoflurane and oxygen. Atracurium 0.5 mg/kg
was given and intubation was performed 3 min later.
Anesthesia was maintained with 1% sevoflurane
in FiO2 0.5 oxygen/nitrous oxide during study and
depended on attending anesthesiologist thereafter.
Additional doses of fentanyl, atracurium, and rate of
Ringer’s acetate infusion were also at the discretion
of the attending anesthesiologist. Before intubation,
tympanic temperature, index temperature, blood
pressure were recorded preinduction (Pre-in) and at
2.5 min after induction (Post-in). Immediately after
intubation (T0), an esophageal temperature probe was
installed and esophageal temperature, tympanic
temperature, index temperature, and blood pressure
were recorded. After intubation esophageal
temperature, index temperature, and blood pressure
were recorded at 15 min intervals (T0, T1, …, T120).
If during the study, systolic blood pressure fell below
90 mmHg then 300 mL of Ringer’s acetate would be
loaded and 2.5 min later blood pressure would be
remeasured. If systolic blood pressure remained below
90 mmHg, the patient would be recorded as having
hypotension. Then 3 mg of ephedrine would be given
and blood pressure would be remeasured at every
2.5 min until systolic blood pressure rose higher than
90 mmHg. If esophageal temperature fell below
35°C, the patient would be warmed using a forced-air
warmer. If ephedrine was given because of
hypotension or a forced-air warmer was applied, data
collected subsequently would not be analyzed. At
90 min and 120 min after intubation, the amount of
intravenous fluid infused, blood loss, total fentanyl, and
ephedrine given were recorded. Data collection ceased
at 120 min after intubation or after skin suturing was
completed. The attending anesthesiologist collected
all data. The primary outcome was to demonstrate a
difference in esophageal temperature between the
groups.
Based on a previous study [8], sample size was
calculated with an α error of 0.5 and power of 80%.
A sample size power calculation determined that 12
patients were needed in each group. A further 20%
of participants were added for dropout, resulted
in 15 patient participants per group and total of
30 participants.
All results were analyzed using IBM SPSS
Statistics for Windows (version 20.0, IBM Corp,
Armonk, NY, USA). According to the results from a
Shapiro–Wilk normality test, parametric data (e.g. age,
body weight, height, all measured temperatures)
were summarized by mean and standard deviation,
where nonparametric data (e.g. blood loss and
anesthesia time) by median and range, and categorical
data by number with percentage. Parametric and
nonparametric data were compared using a t test
and Mann–Whitney U test respectively, whereas
categorical data were compared using a chi-squared
or Fisher’s exact test. Interval parametric data (e.g.
SBP, DBP, temperatures) were compared using a
repeated measures ANOVA. P < 0.05 was considered
significant.
Results
All demographic and perioperative data are
shown in Table 1. All operations exceeded 90 min
postintubation, but only 22 operations, 11 in control
group and 11 in ephedrine group, had exceeded 120
min. During the 90−120 min postintubation period, 3
patients in control group had hypothermia, forced-air
warmer was applied and temperature was not further
recorded. One of the 3 patients also had hypotension,
12 mg of ephedrine was administered and blood
Vol. 9 No. 3 Ephedrine and propofol for induction of anesthesia 381
June 2015

pressure was not further recorded. Because there
was change in sample size to less than calculated
after T105, data at T105 and T120 are listed, but not
analyzed. No significant difference in patient
characteristics, operating room temperature, operation
time, blood loss and total amount of fentanyl
were found. However, total intravenous fluid was
significantly less in the ephedrine group than in the
control group at both 90 min (T90) and 120 min (T120)
after intubation. No patient developed hypotension
in the first 90 min, but 1 patient in the control group
had hypotension during the 90 to 120 min period. No
significant difference in preinduction blood pressure,
tympanic, or index temperature was found.
From after induction to the immediate
postintubation period, tympanic membrane
temperature did not change significantly from baseline
at preinduction in either group. After intubation
esophageal temperature gradually declined in both
groups and became significant when compared
with immediate post-intubation (T0) after T15 for
control group, and T30 for ephedrine group. When
compared between groups, esophageal temperature
was significantly higher in the ephedrine group start
from T60 to T90. Index temperature, when compared
between groups, was significantly higher in the
ephedrine group only at post-induction 2.5 min and
T0. The index temperature was highest at T15 in
the ephedrine group and at T30 in control group
(Table 2).
After induction systolic blood pressure in the
ephedrine group tended to rise and became
significantly higher at T0 then significantly fell to below
preinduction from T15 to T30. In control group,
systolic blood pressure was significantly lower than
preinduction at 2.5 min after induction, from T15 to
T45, and at T75. When compared between groups,
significant differences in systolic blood pressure were
found from 2.5 min after induction to T15. Diastolic
blood pressure also showed similar pattern (Table 3,
Figures 1-3).

Table 1. Patient characteristics and preoperative data

Control Ephedrine P
(n = 15) (n = 15)

Sex, female/male, n 11/4 12/3 >0.999

Age, y 33.8 ± 11.3 30.3 ± 9.9 0.38
BMI 21.9 ± 3.2 21.8 ± 3.8 0.87
Operating room temperature, °C 21.1 ± 0.9 20.8 ± 1.2 0.42
Anesthesia time, min (median [range]) 145 [95−290] 135 [90−405] 0.39
At 90 min
Hypotension, n 0 0 –
IV fluid, mL 963 ± 418 660 ± 219 0.02*
Blood loss, mL (median [range]) 20 [5−500] 40 [5−250] 0.41
Fentanyl, μg (median [range]) 100 [50−250] 100 [50−150] 0.38
At 120 min
Hypotension, n 1 0 >0.999
IV fluid, mL 1235 ± 578 (n = 11) 762 ± 245 (n = 11) 0.02*
Blood loss, mL (median [range]) 20 [5−500] (n = 11) 50 [5–250] (n = 11) 0.52
Fentanyl, μg (median [range]) 100 [50–300] (n = 11) 100 [50–150] (n = 11) 0.22

Values are the mean ± SD, unless specified, *P < 0.05 statistical significance
382 T. Pravitharangul, et al.

Table 2. Comparing temperature between groups

Temperature Control Ephedrine P Temperature Control Ephedrine P

(n = 15) (n = 15) (n = 15) (n = 15)
Tympanic 0.38 Index 0.03*
Pre-in 36.6 ± 0.45 36.7 ± 0.5 0.55 Pre-in 26.7 ± 2.1 27.99 ± 2.49 0.15
Post-in 36.4 ± 0.42 36.7 ± 0.5 0.099 Post-in 27.9 ± 2.6 30.53 ± 2.55 0.01*
T0 36.4 ± 0.7 36.5 ± 0.5 0.83
Esophageal 0.03* T0 29.7 ± 2.8 31.96 ± 2.52 0.03*
T0 36.3 ± 0.3 36.4 ± 0.4 0.51
T15 35.9 ± 0.4 36.2 ± 0.4 0.13 T15 32.7 ± 1.7 33.31 ± 2.45 0.47
T30 35.8 ± 0.5 36.0 ± 0.4 0.11 T30 33.0 ± 1.8 33.05 ± 1.89 0.97
T45 35.7 ± 0.4 35.9 ± 0.4 0.09 T45 32.3 ± 2.6 32.80 ± 1.70 0.49
T60 35.5 ± 0.4 35.9 ± 0.4 0.02* T60 30.5 ± 3.8 32.49 ± 2.19 0.06
T75 35.5 ± 0.4 35.9 ± 0.4 0.01* T75 29.8 ± 4.1 31.60 ± 2.48 0.16
T90 35.4 ± 0.4 35.9 ± 0.4 0.006* T90 28.8 ± 4.3 31.13 ± 2.90 0.09
T105 35.6 ± 0.4 35.9 ± 0.5 T105 29.3 ± 3.5 31.78 ± 3.29
(n = 8) (n = 11) (n = 8) (n = 11)
T120 35.6 ± 0.4 35.9 ± 0.6 T120 29.7 ± 4.3 32.62 ± 2.21
(n = 8) (n = 11) (n = 8) (n = 11)

Values are the mean ± SD, *P < 0.05 statistical significance, Pre-in = pre-induction, Post-in = post-induction 2.5 min, T0, 15,
30, …, 120 = At 0, 15, 30, …, 120 min after intubation

Table 3. Comparing systolic and diastolic blood pressure between groups

Systolic Control Ephedrine P Diastolic Control Ephedrine P

pressure (n = 15) (n = 15) pressure (n = 15) (n = 15)

0.006* 0.046*
Pre-in 120.4 ± 16.1 120.9 ± 13.5 0.92 Pre-in 72.9 ± 7.6 75.4 ± 11.7 0.49
Post-in 91.0 ± 10.6 125.5 ± 14.5 <0.001* Post-in 51.1 ± 8.4 73.3 ± 12.7 <0.001*
T0 121.1 ± 19.9 142.5 ± 25.9 0.02* T0 78.9 ± 16.7 85.6 ± 17.7 0.30
T15 97.0 ± 10.0 111.0 ± 11.7 0.001* T15 59.5 ± 9.2 65.5 ± 14.7 0.19
T30 104.4 ± 15.4 109.5 ± 10.7 0.30 T30 68.1 ± 12.4 63.7 ± 10.8 0.30
T45 107.7 ± 15.2 113.7 ± 15.9 0.30 T45 70.2 ± 15.4 67.1 ± 10.5 0.53
T60 109.9 ± 12.3 113.01 ± 12.5 0.49 T60 70.3 ± 14.5 69.1 ± 12.6 0.81
T75 108.3 ± 12.5 120.5 ± 19.2 0.048* T75 70.6 ± 12.1 73.2 ± 12.4 0.45
T90 113.2 ± 15.4 118.6 ± 12.1 0.30 T90 72.7 ± 15.3 70.3 ± 13.7 0.65
T105 114.5 ± 16.6 114.9 ± 13.0 T105 74.9 ± 11.7 67.6 ± 10.7
(n = 10) (n = 11) (n = 10) (n = 11)
T120 118.0 ± 14.6 112.9 ± 11.8 T120 76.3 ± 14.6 66.5 ± 12.5
(n = 10) (n = 11) (n = 10) (n = 11)

Values are the mean ± SD, *P < 0.05 statistical significance, Pre-in = pre-induction, Post-in = post-induction 2.5 min, T0, 15,
30,…, 120 = At 0, 15, 30,…, 120 min after intubation
Vol. 9 No. 3 Ephedrine and propofol for induction of anesthesia 383
June 2015

Figure 1. Systolic blood pressure and diastolic blood pressure by group. Open circles indicate the ephedrine group, and
solid circles indicate the control group. Data are mean with standard error of mean, *P < 0.05 (between groups),
P < 0.05 (within group from Pre-in), Pre-in = pre-induction, Post-in = post-induction 2.5 min, T0, 15, 30, …,
120 = at 0, 15, 30, …, 120 min after intubation.

Figure 2. Index temperature by group. Open circles indicate the ephedrine group, and solid circles indicate the control
group. Data are mean with standard error of mean, *P < 0.05 (between groups), P < 0.05 (from Pre-in), Pre-in =
pre-induction, Post-in = post-induction 2.5 min, T0, 15, 30, …,120 = at 0, 15, 30, …, 120 min after intubation.
384 T. Pravitharangul, et al.

Figure 3. Tympanic and esophageal temperature by group. Tympanic temperatures are represented by circles and
esophageal temperatures are represented by triangles. Open symbols indicate the ephedrine group, and solid
symbols indicate the control group. Data are mean with standard error of mean, *P < 0.05 (between groups),
P < 0.05 (from Pre-in by tympanic temperature) none, P < 0.05 (from Post-in by esophageal temperature),
Pre-in = pre-induction, Post-in = post-induction 2.5 min, T0, 15, 30, …, 120 = at 0, 15, 30, …, 120 min after
intubation.

Discussion More stable hemodynamics have been reported

The current study suggested that ephedrine
administered as bolus dose during induction is effective
in preventing core temperature loss in plastic and
breast surgery. The mixture of 12 mg of ephedrine
and 2 mg/kg of propofol used results in a mild increase
in blood pressure after induction, which was only
significant immediately after intubation, and then fell
below baseline to a lesser degree when compared
with a mixture of propofol and normal saline.
Previously, successful treatment of cyclical
hypothermia with ephedrine had been reported [9].
Jo et al. also reported the core temperature conserving
property of ephedrine when infused continuously
after intubation in spine surgery with no significant
hypertension [8].
The increase in index temperature after
induction in both groups suggested the effect of heat
redistribution. Faster time-to-peak in the ephedrine
group suggests an increase in cardiac output while
the early decline suggests a vasoconstriction effect.
Both esophageal and index temperature tended
to be higher in the ephedrine group. This might be
partly result from increasing metabolism or from the
β-adrenergic agonist effect of ephedrine [10].
for combined ephedrine with propofol. Less
hypotension with no significant hypertension was found
when 0.15 mg/kg ephedrine was combined with 2.5
mg/kg of propofol, and 3 μg/kg of remifentanil [7]. A
similar profile can be seen in this study except for the
significant increase in blood pressure at immediate
after intubation, which might result from the difference
in anesthetic agents and doses.
Some of limitations of this study should be
considered. An esophageal temperature probe
was not fitted before intubation because of
patient discomfort. By using tympanic membrane
temperature, the trend of core temperature change
can be demonstrated, but may not be a reliable
substitute for baseline. The amount of fluid infused
was determined by the attending anesthesiologist.
Therefore, all fluid was warmed to 41°C to minimize
the effect of cold fluid. Finally, plastic surgery varies
in sites of operation and exposures may affect heat
loss and skin temperature monitoring.
Conclusion
Induction of general anesthesia with mixture of
ephedrine and propofol can decrease core temperature
Vol. 9 No. 3 Ephedrine and propofol for induction of anesthesia
June 2015
loss during plastic and breast surgery compared with
propofol alone.
Acknowledgments
This study was supported by departmental and
institutional funding only.
Conflict of interest statement
The authors have no conflicts of interest to
declare.
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